Triggered liposomal release

Wu G, Mikhailovsky A, Khant HA et al (2008) Remotely triggered liposome release by near-infrared light absorption via hollow gold nanoshells. J Am Chem Soc 130 8175-8177... 

Key words Triggered liposomal release. Membrane channel protein, Mechanosensitive channel of... 

The chemical modification of MscL requires a free cysteine residue at a critical part of the channel, namely the 22nd amino acid. A 6-histidine(His) tag at the C-terminal of the protein allows a one-step isolation of MscL, which is >98% pure as analyzed by SDS-PAGE and N-terminal sequencing. The protein can be labeled in its pure isolated form, or alternatively, in its nickel-nitriloacetic acid (Ni-NTA) column-attached form. ESI-MS is a method to follow the labeling conditions and efficiency. After the protein is chemically labeled and reconstituted into desired liposomes, a simple fluorescent, dye efflux experiment is used to test the triggered liposomal release. 

In addition to enzymatic hydrolysis of natural lipids in polymeric membranes as discussed in chapter 4.2.2., other methods have been applied to trigger the release of vesicle-entrapped compounds as depicted in Fig. 37. Based on the investigations of phase-separated and only partially polymerized mixed liposomes 101, methods to uncork polymeric vesicles have been developed. One specific approach makes use of cleavable lipids such as the cystine derivative (63). From this fluorocarbon lipid mixed liposomes with the polymerizable dienoic acid-containing sulfolipid (58) were prepared in a molar ratio of 1 9 101115>. After polymerization of the matrix forming sulfolipids, stable spherically shaped vesicles are obtained as demonstrated in Fig. 54 by scanning electron microscopy 114>. 

Kong, G., Anyarambhatla, G., Petros, W.P, et al. Efficacy of liposomes and hyperthermia in a human tumor xenograft model Importance of triggered drug release. Cancer Res. 60(24) 6950-6957. 2000. 

The acidification of endosomal compartments, as they evolve toward lysosomes is a well-described phenomenon (1) that can be exploited to design drug delivery systems capable of releasing their contents after endocytosis. Enhanced cytoplasmic drug concentrations can therefore be achieved with smart formulations, which are sensitive to acidic pHs. For this purpose, liposomal formulations are attractive, because their deformable phospholipid bilayers can be rapidly disrupted to trigger drug release. In this section, ionizable copolymers of ISTisopropylacrylamide (NIPAM) are anchored in the phospholipid membrane and used to destabilize the bilayer upon acidification of the environment. 

This chapter thoroughly describes the preparation of poly(NIPAM-co-MAA)-based liposomes that can enhance the cytoplasmic bioavailability of drugs by triggering drug release, specifically, in acidic compartments. The optimization and characterization of these systems have been described in numerous publications (3-9). 

A. Kocer, A remote controlled valve in hposomes for triggered hposomal release, J. Liposome Res., 2007, 17, 219-225. 

The study demonstrates that liposomes surface-modified with A-(2-hydroxypropyl)methacrylamide (HPMA) mono/dilactate copolymer are attractive systems for achieving temperature-triggered content release... 

Paasonen L, Romberg B, Storm G, Yliperttula M, Urtti A, Hennink WE (2007) Temperature-senstive poly (N-(2-hydroxypropyl) methacrylamide mono/dilactat)-coated liposomes for triggered contents release. Bioconjug Chem 18 2131-2136... 

Shin J, Shum P, Thompson D. Acid-triggered release via dePEGylation of DOPE liposomes containing acid-labile vinyl ether PEG-lipids. J Contr Rel 2003 91 187. 

Ishida T, et al. Targeted delivery and triggered release of liposomal doxorubicin enhances cytotoxicity against human B l5miphoma cells. Biochim Biophys Acta 2001 1515 144. 

Antonsson, B., Montessuit, S., Lauper, S., Eskes, R., and Martinou, J. C., 2000, Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria, Biochem. J. 345 Part 2, pp. 271-278... 

Andresen TL, Jensen SS, Kaasgaard T, Jorgensen K. Triggered activation and release of liposomal prodmgs and drugs in cancer tissue by secretory phospholipase A2. Curr Drug Deliv. 2005 2 353-362. 

Venugopalan P, Jain S, Sankar S, Singh P, Rawat A, Vyas SP (2002) pH-sensitive liposomes mechanism of triggered release to drug and gene delivery prospects. Pharmazie 57( 10) 659-671... 

The transition from coated vesicle to early endosome is accompanied by acidification of the vesicular lumen that continues into the late endosomal and lysosomal compartments, reaching a final pH in the perinuclear lysosome of approximately 4.5. Such acidification associated with endosome maturation provides the means by which certain viruses gain access to the cytosol. Acid-induced conformational changes in the viral proteins trigger translocation across the endosomal membrane via a fusion process. By taking advantage of the endosomal acidification, pH-sensitive liposomes, adenovirus and endosomolytic peptides have been used to facilitate the release of plasmids into the cytoplasm prior to lysosomal degradation. 

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